Association of Tenofovir Use With Risk of Incident Heart Failure in HIV‐Infected Patients

BACKGROUND: The antiretroviral medication, tenofovir disoproxil fumarate (TDF), is used by most human immunodeficiency virus–infected persons in the United States despite higher risks of chronic kidney disease. Although chronic kidney disease is a strong risk factor for heart failure (HF), the association of TDF with incident HF is unclear. METHODS AND RESULTS: We identified 21 435 human immunodeficiency virus–infected patients in the United States Veterans Health Administration actively using antiretrovirals between 2002 and 2011. We excluded patients with a prior diagnosis of HF. TDF was analyzed categorically (current, past, or never use) and continuously (per year of use). Proportional hazards regression and fully adjusted marginal structural models were used to determine the association of TDF exposure with risk of incident HF after adjustment for demographic, human immunodeficiency virus–related, and cardiovascular risk factors. During follow‐up, 438 incident HF events occurred. Unadjusted 5‐year event rates for current, past, and never users of TDF were 0.9 (95%CI 0.7‐1.1), 1.7 (1.4‐2.2), and 4.5 (3.9‐5.0), respectively. In fully adjusted analyses, HF risk was markedly lower in current TDF users (HR=0.68; 95%CI 0.53‐0.86) compared with never users. Among current TDF users, each additional year of TDF exposure was associated with a 21% lower risk of incident HF (95%CI: 0.68‐0.92). When limited to antiretroviral‐naive patients, HF risk remained lower in current TDF users (HR=0.53; 95%CI 0.36‐0.78) compared to never users. CONCLUSIONS: Among a large national cohort of human immunodeficiency virus–infected patients, TDF use was strongly associated with lower risk of incident HF. These findings warrant confirmation in other populations, both with TDF and the recently approved tenofovir alafenamide fumarate.